Although motor difficulties are the most prominent symptoms of Parkinson's disease (PD), cognitive disturbances are also found in most patients. In non-demented patients, most of the cognitive disturbances resemble those seen in patients with frontal lobe disorders. These cognitive disorders are not as responsive to anti-parkinsonian drug therapies as are the motor symptoms of the disease and may become a source of great concern to patients and their families. There presently does not exist an adequate model for the study of these types of cognitive disorders. The proposed research will fill this void by utilizing a model of "early" parkinsonism in the primate: produced by chronic, low dose exposured MVTP. This produces animals asymptomatic for a parkinsonian motor disorder, but with distinct cognitive disturbances. Using this model, we will further explore the nature of cognitive disturbances in these animals and assess their similarity to those found in human PD patients, attempt to reverse the deficits pharmacologically, and examine in detail the neurochemistry and pathology of cortical and subcortical brain regions in an attempt to determine the physiological basis for the behavioral disturbances. The work proposed in this application represents an area of research which is virtually non-existent at this point in time. The chronic, low dose MPTP exposure model which we have developed in our laboratory is a powerful tool for studying the effects of fairly extensive damage to ascending catecholaminergic systems on behavior without the confound of a motor disorder. This research will greatly further our understanding of the cognitive deficits which accompany parkinsonism and may lead to new therapeutic strategies for their treatment This research will also provide new information on the role of the striatum in cognition. The proposed work should be of interest to neurologists and neuropsychologists as well as basic neuroscientists.